Timing of initiation of renal replacement therapy for acute kidney injury

What is the issue?

Acute kidney injury (AKI) is very common among patients admitted to intensive care unit (ICU); it is associated with high death rates and characterised by the rapid loss of the kidney function. Patients with AKI show increased levels of serum uraemic toxins (creatinine and urea), serum potassium and metabolic acids, accumulation of water and in the most cases a reduction in urine output. In this population these chemicals and fluid overload are related to increased rates of death. Theoretically, early removal of toxins and excess water from the bloodstream might improve patient outcomes (such as death rate and recovery of kidney function).

Renal replacement therapy (RRT) is a blood purification technique that enables removal of excess water and toxins. RRT involves blood being diverted from the patient via a catheter (a hollow, flexible tube placed into a vein) through a filtering system which removes excess water and toxins; purified blood is then returned to the patient via the catheter. Early initiation of RRT improves the removal of toxins and excess water. The aim of this review was to investigate the effect of different timing of RRT initiation (early or standard) on death, recovery of kidney function, and adverse events in people with AKI who are critically ill.

What did we do?

We searched the literature up until August 2018 and identified five studies enrolling 1084 critically ill patients with AKI that were evaluated in this review.

What did we find?

Five randomised studies enrolling 1084 participants were included in our review. Compared to standard, early initiation of RRT may reduce the risk of death, may increase the recovery of kidney function, or increase the risk of adverse events in patients with AKI in intensive care units. Nevertheless, in death the early initiation of RRT showed a range of values that included benefit (decrease death), as well as harm (increase death).

Authors' conclusions: 

Based mainly on low quality of evidence identified, early RRT may reduce the risk of death and may improve the recovery of kidney function in critically patients with AKI, however the 95% CI indicates that early RRT might worsen these outcomes. There was an increased risk of adverse events with early RRT. Further adequate-powered RCTs using appropriate criteria to define the optimal time of RRT are needed to reduce the imprecision of the results.

Read the full abstract...

Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs), and is associated with high death. Renal replacement therapy (RRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate RRT so as to improve clinical outcomes remains uncertain.

This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury.


To assess the effects of different timing (early and standard) of RRT initiation on death and recovery of kidney function in critically ill patients with AKI.

Search strategy: 

We searched the Cochrane Kidney and Transplant’s Specialised Register to 23 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 11 September 2017.

Selection criteria: 

We included all randomised controlled trials (RCTs). We included all patients with AKI in ICU regardless of age, comparing early versus standard RRT initiation. For safety and cost outcomes we planned to include cohort studies and non-RCTs.

Data collection and analysis: 

Data were extracted independently by two authors. The random-effects model was used and results were reported as risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).

Main results: 

We included five studies enrolling 1084 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early initiation may reduce the risk of death at day 30, although the 95% CI does not rule out an increased risk (5 studies, 1084 participants: RR 0.83, 95% CI 0.61 to 1.13; I2 = 52%; low certainty evidence); and probably reduces the death after 30 days post randomisation (4 studies, 1056 participants: RR 0.92, 95% CI 0.76 to 1.10; I2= 29%; moderate certainty evidence); however in both results the CIs included a reduction and an increase of death. Earlier start may reduce the risk of death or non-recovery kidney function (5 studies, 1076 participants: RR 0.83, 95% CI 0.66 to 1.05; I2= 54%; low certainty evidence). Early strategy may increase the number of patients who were free of RRT after RRT discontinuation (5 studies, 1084 participants: RR 1.13, 95% CI 0.91 to 1.40; I2= 58%; low certainty evidence) and probably slightly increases the recovery of kidney function among survivors who discontinued RRT after day 30 (5 studies, 572 participants: RR 1.03, 95% CI 1.00 to 1.06; I2= 0%; moderate certainty evidence) compared to standard; however the lower limit of CI includes the null effect. Early RRT initiation increased the number of patients who experienced adverse events (4 studies, 899 participants: RR 1.10, 95% CI 1.03 to 1.16; I2 = 0%; high certainty evidence). Compared to standard, earlier RRT start may reduce the number of days in ICU (4 studies, 1056 participants: MD -1.78 days, 95% CI -3.70 to 0.13; I2 = 90%; low certainty evidence), but the CI included benefit and harm.